When the copolymerization of vinylidene fluoride (VDF) and hexafluoropropylene (HFP) is carried out in super-critical carbon dioxide (scCO(2)) under heterogeneous conditions, the reaction occurs both in the continuous CO2-rich phase and in the dispersed polymer-rich phase. The two phases being characterized by different values of reactant concentrations and kinetic parameters, one would expect that the reaction kinetics is affected by the polymer phase holdup in the reactor. However, the reaction rate is almost insensitive to the amount of produced polymer, at least at specific reaction conditions. This apparent contradiction is discussed and clarified in this paper by a series of comparative simulations carried out using different models, accounting for the reaction in one single phase (one-locus) or in two phases (two-loci). This analysis provides general procedures which can be used to design experimental investigations able to identify the number of reaction loci for a given heterogeneous polymerization system. POLYM. ENG. SCI., 51:2093-2102, 2011. (C) 2011 Society of Plastics Engineers